Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer, with more than 900,000 cases diagnosed each year, and is one of the major causes of cancer death worldwide (Sankaranarayanan, et al., 1998). In the United States alone, 50,000 new cases and 8,000 deaths are reported each year (Greeenlee, et al., 2000). It affects the oral cavity, the oropharynx, the larynx, and the hypopharynx (Mashberg, et al., 1993). Tobacco carcinogens are believed to be the primary etiologic agents of the disease, with alcohol consumption, age, gender, and ethnic background as contributing factors (Hu, et al., 2007). There is no known inherited form of the disease, however mutations of several well documented tumor associated genes have been described in HNSCC (Zimmermann, et al., 2007; Righini, et al., 2007; Ohshiro, et al., 2007; Chai, et al., 2006; Brailo, et al., 2006).
Although surgery and radiotherapy are highly effective treatments for HNSCC early-stage disease (stage I or II), with cure rates ranging from 70% to 85%, advanced disease (stage III or IV) remains difficult to control, with an estimated 5-year survival rate of 30% to 40% (Vokes, et al., 1993). Therefore, prevention and early diagnosis of high-risk premalignant lesions are high priorities for reducing morbidity and mortality in head and neck cancer. In addition, regional metastasis is an important factor in the prognosis and choice of treatment for patients with HNSCC. The presence of nodal metastasis significantly affects the survival of the patient.
The molecular mechanisms for the progression of HNSCC cancers are not well understood but are widely believed to involve alcohol, tobacco and deregulation of growth factors leading to development of cancer (Boyle, et al., 1993 and Brachman, et al., 1994). Microarray data shows elevation of IL-8, IL-6, VEGF, MMP-9, TGF-B, MMP-7, plasminogen activated (PA), uPA, IGF and INF-2 proteins in HNSCC (unpublished data). The expression of these proteins increases as the disease progresses and thus, appears to have a direct role in the development of HNSCC. The proteins are also shown to be elevated in persons who smoke or drink heavily, but do not have HNSCC.